A reliable, quantitative and noninvasive method for the characterization of the molecular changes associated with early cataractogenesis in vivo has long been an important goal of human clinical cataract research. Such a method would allow researchers and physicians to (a) assess the effectiveness of putative anticataract reagents; (b) evaluate the cataractogenic role of pharmacologic agents or radiation used in the treatment of systematic diseases; (c) characterize early cataract in epidemiologic studies of human or animal populations subject to differential cataractogenic stress; and (d) provide a quantitative basis for the medical decision to intervene surgically or pharmaceutically in the treatment of cataract.
In 1975, T. Tanaka and G. Benedek ("Observation of Protein Diffusivity in Intact Human and Bovine Lenses with Application to Cataract," Invest. Opthal, 14, 1985, pp. 449-456) showed that the Brownian motion of proteins in excised human and bovine lenses could be measured optically using the method of quasielastic light scattering (QLS) spectroscopy. Following this work, T. Tanaka and C. Ishimoto ("In Vivo Observation of Lens Protein Diffusivity in Normal and X-Irradiated Rabbit Lenses," Exp. Eye Res., 39, 1984, pp. 61-68) demonstrated that QLS could be used in vivo in the rabbit to detect changes in mean protein diffusivity as a function of age and position in the lens. Further observations showed that the cataractogenic insult of x-irradiation upon the rabbit lens produced dramatic changes in the form of the autocorrelation function of the scattered light at a very early stage in the cataractogenic process. The autocorrelation function is an important tool for mathematical analysis of QLS. This change in the autocorrelation function demonstrated that the x-irradiation was responsible for drastic changes in the diffusivity of the protein scattering elements undergoing Brownian movement within the ocular tissue. Both Nishio and the 1977 Tanaka team observed that these altered correlation functions had a form different from that expected for the Brownian motions of a single-type scatterer. However, neither understood a quantitative analysis of the information contained in the non-exponential character of the autocorrelation function observed.
In 1986, T. Libondi et al. ("In Vivo Measurement of the Aging Rabbit Lens Using Quasielastic Light Gathering," Curr. Eye. Res., Vol. 5, No. 6, 1986, pp. 411-419) showed that the form of the autocorrelation function of the scattered light from a living rabbit eye indicated the presence of at least two distinct diffusing aspects within the rabbit lens. One species had a diffusivity corresponding to the .alpha.-crystalline protein. The other was a much more slowly diffusing species of the type discovered in vitro by M. Delaye et al. ("Identification of the Scattering Elements Responsible for Lens Opacification in Cold Cataracts," Biophys. J., 37, 1982, pp. 647-656).
A recently discovered method of cataract detection comprises irradiating a measurement location of a lens with a laser and collecting the light scattered from the lens at the measurement location. The collected light is then analyzed using an autocorelator or spectrum analyzer to determine the relative amount of light scattered from different protein scatterers in the lens, and the relative light data are analyzed to determine the degree of cataract formation at the measurement location in the lens. A more detailed description of the method is given in U.S. Pat. No. 4,957,113, issued Sep. 18, 1990, which is incorporated herein by reference. However, in situations where the lens contains a significant amount of immobile protein species, this method is not suitable.